1. Field of the Invention
The present invention relates to pharmaceutical compositions which inhibit the onset or progress of liver cancer. Particularly, the present invention relates to pharmaceutical compositions which inhibit the onset or progress of liver cancer in patients with hepatitis or liver cirrhosis. The present invention also relates to health-promoting foods which are effective for inhibiting the onset or progress of liver cancer in patients with hepatitis or liver cirrhosis. The present invention further relates to methods for inhibiting the onset or progress of liver cancer by administering such a composition.
2. Discussion of the Background
The mechanism of the progress from hepatitis or liver cirrhosis to liver cancer has not been entirely elucidated. To inhibit liver cancer, however, it is considered important to remove the etiology of hepatitis or liver cirrhosis.
For example, it has been reported that removal of hepatitis virus by interferon treatment significantly inhibits carcinogenesis (Ann. Intern. Med., vol. 129, p. 94 (1998)). As a method for removing hepatitis virus, a treatment using an antiviral drug can be mentioned (N. Engl. J. Med., vol. 339, p. 1485 (1998) and J. Viral Hepatitis. vol. 3, p. 211 (1996)). In any event, it is not possible to remove the virus from all patients, and complete prophylaxis of liver cancer has not been achieved.
While attempts have been made to inhibit liver cancer by inhibiting chronic inflammation with a liver protecting agent and the like, liver cancer cannot be prevented entirely (Cancer, vol. 76, p. 743 (1995) and Cancer, vol. 79, p. 1494 (1997)).
Furthermore, while the treatment or inhibition of cancer by deficiency or excessive administration of particular amino acids, such as methionine deficiency, valine deficiency, aspartic acid deficiency, lysine deficiency, cystine deficiency, phenylalanine deficiency, increased administration of arginine, increased administration of glutamine and the like, has been also tried, the situation is by no means satisfactory (JJPEN (1997) 19:195-199 and “Japanese Journal of Nutritional Assessment” (1992) vol. 9 No. 2 p. 142-146).
Meanwhile, some patients with liver cirrhosis exhibit an accompanying decrease in blood Fischer ratio (branched chain amino acid mol (isoleucine+leucine+valine)/aromatic amino acid mol (phenylalanine+tyrosine)) and a decrease in serum albumin concentration, which are caused by an abnormality in the metabolism of protein and/or amino acid. The serum albumin concentration and Fischer ratio in these cases show a positive correlation (Japan Medical Journal, vol. 3101, p. 3 (1983)), and lower serum albumin concentration is known to cause shortened life expectancy (JJPEN (1995) 17:1135).
To improve hypoalbuminemia caused by disorders of amino acid metabolism in patients with liver cirrhosis, administration of a branched chain amino acid (BCAA) combination preparation called LIVACT (registered trademark) has been employed.
As for AMINOLEBAN EN (registered trademark), which is a nutritional status improving drug for patients with chronic hepatic failure associated with liver encephalopathy, it has been reported that administration of a feed containing this drug to rats with chemical-induced liver cancer revealed a tendency to inhibit liver cancer as compared to a control group bred on a conventional feed (Japanese Journal of Nutritional Assessment (1992) vol. 9 No. 2 p. 142-146). However, this reference does not at all suggest that such carcinogenesis inhibitory effect is related to a particular component in AMINOLEBAN EN (registered trademark), which is a balanced nutrition product containing carbohydrates, protein and fat, supplemented with various vitamins and minerals.
Similarly, it has been reported that long-term administration of a BCAA added feed to LEC rats (spontaneous carcinogenesis model) exhibited an inhibitory action on the progress of cancer, though the incidence of cancer did not vary from that of the control group (Acta Hepatologica Japonica (2002) 43 Supplement(2): A359). However, this reference does not describe the kind of BCAA, the mixing ratio and the like, nor does it suggest that such action is related to a particular component in BCAA.
The aforementioned LIVACT (registered trademark) is a preparation consisting of three kinds of branched chain amino acids of isoleucine, leucine, and valine, which was developed for the purpose of correcting the Fischer ratio, increasing serum albumin concentration and improving clinical conditions, by orally supplementing these branched chain amino acids at an appropriate ratio. However, its action to inhibit carcinogenesis is not known. The technical relationship between hypoalbuminemia and cancer onset has not been known, either.
Thus, there remains a need for compositions and methods for inhibiting the onset or progress of liver cancer